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Escherichia coli K-12 substr. MG1655 Pathway: threonine degradation I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Degradation/Utilization/Assimilation Amino Acids Degradation Threonine Degradation

Summary:
General Background

Microorganisms and mammals share two of the major, initial routes for threonine degradation. In the first route threonine is catabolized by catabolic threonine dehydratase (EC 4.3.1.19) to ammonia and 2-oxobutanoate. A biosynthetic version of this enzyme also occurs (see threonine deaminase) [Umbarger57]. In the second route threonine is catabolized by threonine dehydrogenase (EC 1.1.1.103) to form 2-amino-3-oxobutanoate, which is mainly cleaved by 2-amino-3-ketobutyrate CoA ligase, forming glycine and acetyl-CoA. The 2-amino-3-oxobutanoate can also be spontaneously converted to aminoacetone, which may be further metabolized to methylglyoxal (see threonine degradation III (to methylglyoxal)). A third route has been demonstrated in several bacteria and fungi. This route is based on the enzyme low-specificity L-threonine aldolase (EC 4.1.2.5), which cleaves threonine directly into glycine and acetaldehyde.

Escherichia. coli has been shown to assimilate nitrogen from some (but not all) amino acids, as well as agmatine, γ-aminobutyrate and the polyamines putrescine and spermidine. These nitrogen sources are used to generate glutamate and glutamine, the major intracellular nitrogen donors. Some nitrogen sources, such as aspartate, can generate glutamate by transamination (see aspartate aminotransferase, PLP-dependent). Others, such as proline and arginine, produce glutamate as end products (glutamate generating amino acids) (see proline degradation and arginine degradation II (AST pathway)). Other nitrogen sources, such as serine, require ammonia production for glutamate synthesis (ammonia generating amino acids) (see L-serine degradation). Ammonia generation is required for glutamine synthesis (see glutamine biosynthesis I).

In E. coli a low intracellular level of ammonia results in low intracellular glutamine and induction of the nitrogen-regulated (Ntr) response that involves response regulators NtrC transcriptional dual regulator and NtrB sensory histidine kinase. The Ntr response functions in ammonia assimilation, nitrogen scavenging and metabolic coordination.

E. coli has three systems that can transport threonine: serine / threonine:Na+ symporter [Kim02a], branched chain amino acid ABC transporter [Robbins73], and serine / threonine:H+ symporter TdcC [Sumantran90]. Although E. coli can use threonine, glycine, or serine as a nitrogen source, efficient serine or threonine utilization requires amino acid supplementation. Leucine supplementation is required for the use of threonine as a nitrogen source in pathways utilizing threonine dehydrogenase (TDH) which is induced by leucine [Potter77] (see threonine degradation II and threonine degradation III (to methylglyoxal)). TDH is is a major route for threonine degradation in E. coli. A minor pathway is shown in threonine degradation IV and an anaerobic pathway is shown in threonine degradation I.

Reviews: Reitzer, L. (2005) "Catabolism of Amino Acids and Related Compounds" EcoSal 3.4.7 [ECOSAL] and [Reitzer03]

About This Pathway

Enteric bacteria such as Escherichia coli K-12 and Salmonella enterica subsp. enterica serovar Typhimurium have been shown to possess two types of threonine dehydratases - a catabolic enzyme, which is induced by threonine (see catabolic threonine dehydratase), and a constitutively-produced biosynthetic enzyme (see threonine deaminase) [Umbarger57]. Both enzymes convert threonine to 2-oxobutanoate. While the biosynthetic enzyme is involved in isoleucine biosynthesis (see isoleucine biosynthesis I (from threonine)), the catabolic enzyme participates in the degradation of threonine to propionate in a pathway that generates ATP and enables the utilization of threonine as a sole source of carbon and energy [Luginbuhl74]. This E. coli anaerobic threonine dehydratase pathway is shown here [Sawers98a, Hesslinger98].

The first reaction in this pathway is catalyzed by catabolic threonine dehydratase which degrades threonine to 2-oxobutanoate (α-ketobutyrate) and ammonia. The 2-oxobutanoate then undergoes lyase cleavage with the addition of coenzyme A to form propanoyl-CoA and formate. Two such lyases were discovered in E. coli K-12 [Hesslinger98]. Both of these enzymes, pyruvate formate-lyase / 2-ketobutyrate formate-lyase encoded by gene pflB and 2-ketobutyrate formate-lyase / pyruvate formate-lyase 4 encoded by gene tdcE, are expressed only under anaerobic conditions, and both utilize a glycyl radical as part of their catalytic mechanism [Sawers98b]. TdcE is equally active with 2-oxobutanoate and pyruvate substrates, whereas PflB prefers pyruvate. Once propanoyl-CoA is formed, it is processed via propionyl-phosphate to propionate in a reaction sequence that produces ATP. Acetate kinase AckA can also utilize propionate as a substrate in the final reaction. The enzymes in this pathway are also able to process L-serine, with pyruvate as the final product [Sawers98a].

Features of this energy-generating pathway include substrate-level phosphorylation, a requirement for cAMP-CRP, and catabolite repression. The tdcABCDEFG operon genes also encode serine / threonine:H+ symporter TdcC (see above), L-serine deaminase III, and predicted enamine/imine deaminase. Regulators of the operon include adjacent TdcR DNA-binding transcriptional activator, CRP transcriptional dual regulator, IHF DNA-binding transcriptional dual regulator, and TdcA DNA-binding transcriptional activator. This pathway does not appear to be essential because inactivation of tdcB [Goss84]. tdcE [Hesslinger98], or tdcD [Hesslinger98] resulted in no discernible phenotype.

Reviews: Reitzer, L. (2005) "Catabolism of Amino Acids and Related Compounds" EcoSal 3.4.7 [ECOSAL] and [Simanshu07]

Superpathways: superpathway of threonine metabolism

Variants: threonine degradation II , threonine degradation III (to methylglyoxal) , threonine degradation IV

Credits:
Created 04-Jan-2007 by Caspi R , SRI International
Last-Curated ? 14-Nov-2011 by Fulcher C , SRI International


References

Bell77: Bell SC, Turner JM (1977). "Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium." Biochem J 164(3);579-587. PMID: 16743051

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Goss84: Goss TJ, Datta P (1984). "Escherichia coli K-12 mutation that inactivates biodegradative threonine dehydratase by transposon Tn5 insertion." J Bacteriol 158(3);826-31. PMID: 6327641

Hesslinger98: Hesslinger C, Fairhurst SA, Sawers G (1998). "Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate." Mol Microbiol 1998;27(2);477-92. PMID: 9484901

Kim02a: Kim YM, Ogawa W, Tamai E, Kuroda T, Mizushima T, Tsuchiya T (2002). "Purification, reconstitution, and characterization of Na(+)/serine symporter, SstT, of Escherichia coli." J Biochem (Tokyo) 132(1);71-6. PMID: 12097162

Luginbuhl74: Luginbuhl GH, Hofler JG, Decedue CJ, Burns RO (1974). "Biodegradative L-threonine deaminase of Salmonella typhimurium." J Bacteriol 120(1);559-61. PMID: 4370904

Potter77: Potter R, Kapoor V, Newman EB (1977). "Role of threonine dehydrogenase in Escherichia coli threonine degradation." J Bacteriol 132(2);385-91. PMID: 334738

Reitzer03: Reitzer L (2003). "Nitrogen assimilation and global regulation in Escherichia coli." Annu Rev Microbiol 57;155-76. PMID: 12730324

Robbins73: Robbins JC, Oxender DL (1973). "Transport systems for alanine, serine, and glycine in Escherichia coli K-12." J Bacteriol 1973;116(1);12-8. PMID: 4583203

Sawers98a: Sawers G (1998). "The anaerobic degradation of L-serine and L-threonine in enterobacteria: networks of pathways and regulatory signals." Arch Microbiol 171(1);1-5. PMID: 9871012

Sawers98b: Sawers G, Watson G (1998). "A glycyl radical solution: oxygen-dependent interconversion of pyruvate formate-lyase." Mol Microbiol 1998;29(4);945-54. PMID: 9767563

Shizuta70: Shizuta Y, Hayaishi O (1970). "Regulation of biodegradative threonine deaminase synthesis in Escherichia coli by cyclic adenosine 3',5'-monophosphate." J Biol Chem 245(20);5416-23. PMID: 4319241

Simanshu07: Simanshu DK, Chittori S, Savithri HS, Murthy MR (2007). "Structure and function of enzymes involved in the anaerobic degradation of L-threonine to propionate." J Biosci 32(6);1195-206. PMID: 17954980

Sumantran90: Sumantran VN, Schweizer HP, Datta P (1990). "A novel membrane-associated threonine permease encoded by the tdcC gene of Escherichia coli." J Bacteriol 1990;172(8);4288-94. PMID: 2115866

Umbarger57: Umbarger HE, Brown B (1957). "Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases." J Bacteriol 73(1);105-12. PMID: 13405870

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Avison01: Avison MB, Horton RE, Walsh TR, Bennett PM (2001). "Escherichia coli CreBC is a global regulator of gene expression that responds to growth in minimal media." J Biol Chem 276(29);26955-61. PMID: 11350954

Barak98: Barak R, Abouhamad WN, Eisenbach M (1998). "Both acetate kinase and acetyl coenzyme A synthetase are involved in acetate-stimulated change in the direction of flagellar rotation in Escherichia coli." J Bacteriol 1998;180(4);985-8. PMID: 9473056

Becker02: Becker A, Kabsch W (2002). "X-ray structure of pyruvate formate-lyase in complex with pyruvate and CoA. How the enzyme uses the Cys-418 thiyl radical for pyruvate cleavage." J Biol Chem 277(42);40036-42. PMID: 12163496

Becker99: Becker A, Fritz-Wolf K, Kabsch W, Knappe J, Schultz S, Volker Wagner AF (1999). "Structure and mechanism of the glycyl radical enzyme pyruvate formate-lyase." Nat Struct Biol 6(10);969-75. PMID: 10504733

Blaschkowski82: Blaschkowski HP, Neuer G, Ludwig-Festl M, Knappe J (1982). "Routes of flavodoxin and ferredoxin reduction in Escherichia coli. CoA-acylating pyruvate: flavodoxin and NADPH: flavodoxin oxidoreductases participating in the activation of pyruvate formate-lyase." Eur J Biochem 1982;123(3);563-9. PMID: 7042345

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Brown77: Brown TD, Jones-Mortimer MC, Kornberg HL (1977). "The enzymic interconversion of acetate and acetyl-coenzyme A in Escherichia coli." J Gen Microbiol 1977;102(2);327-36. PMID: 21941

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Calhoun73: Calhoun DH, Rimerman RA, Hatfield GW (1973). "Threonine deaminase from Escherichia coli. I. Purification and properties." J Biol Chem 1973;248(10);3511-6. PMID: 4573981

CamposBermudez10: Campos-Bermudez VA, Bologna FP, Andreo CS, Drincovich MF (2010). "Functional dissection of Escherichia coli phosphotransacetylase structural domains and analysis of key compounds involved in activity regulation." FEBS J 277(8);1957-66. PMID: 20236319

CastanoCerezo09: Castano-Cerezo S, Pastor JM, Renilla S, Bernal V, Iborra JL, Canovas M (2009). "An insight into the role of phosphotransacetylase (pta) and the acetate/acetyl-CoA node in Escherichia coli." Microb Cell Fact 8;54. PMID: 19852855

Chang99: Chang DE, Shin S, Rhee JS, Pan JG (1999). "Acetate metabolism in a pta mutant of Escherichia coli W3110: importance of maintaining acetyl coenzyme A flux for growth and survival." J Bacteriol 181(21);6656-63. PMID: 10542166

Conradt84: Conradt H, Hohmann-Berger M, Hohmann HP, Blaschkowski HP, Knappe J (1984). "Pyruvate formate-lyase (inactive form) and pyruvate formate-lyase activating enzyme of Escherichia coli: isolation and structural properties." Arch Biochem Biophys 1984;228(1);133-42. PMID: 6364987

Datta87: Datta P, Goss TJ, Omnaas JR, Patil RV (1987). "Covalent structure of biodegradative threonine dehydratase of Escherichia coli: homology with other dehydratases." Proc Natl Acad Sci U S A 1987;84(2);393-7. PMID: 3540965

De07: De Mey M, Lequeux GJ, Beauprez JJ, Maertens J, Van Horen E, Soetaert WK, Vanrolleghem PA, Vandamme EJ (2007). "Comparison of different strategies to reduce acetate formation in Escherichia coli." Biotechnol Prog 23(5);1053-63. PMID: 17715942

De07b: De Mey M, De Maeseneire S, Soetaert W, Vandamme E (2007). "Minimizing acetate formation in E. coli fermentations." J Ind Microbiol Biotechnol 34(11);689-700. PMID: 17668256

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Dittrich05: Dittrich CR, Bennett GN, San KY (2005). "Characterization of the acetate-producing pathways in Escherichia coli." Biotechnol Prog 21(4);1062-7. PMID: 16080684

Egan77: Egan RM, Phillips AT (1977). "Requirements for induction of the biodegradative threonine dehydratase in Escherichia coli." J Bacteriol 132(2);370-6. PMID: 334737

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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